Examining 3 Key Studies on Treatments for AML and ALL | Jayastu Senapati, MD, MBBS | #ASH24

It's amazing to be at the 2024 American Society of Hematology meeting at San Diego. A lot of good science being shared. Nice to catch up with other collaborators, industry friends and discuss, hematology in the broader sense and my field of specialty, which is leukemia. I'm Jayastu Senapati, I'm an assistant professor of leukemia at the University of Texas MD Anderson Cancer Center, and I'll be showing some interesting work on which, you know, my research has been at this Ash meeting.

I'll try to speak about 2 to 3 important posters or abstracts, that will be shown in this meeting. The first one pertains to a disease known as core binding factor, acute myeloid leukemia. So acute myeloid leukemia generally are considered high risk leukemias, more commonly in slightly older patients, the median age being above, around the sixth and seventh decade of life.

Core binding factor AML are a smaller subset of AML. Around 20% of AML will actually have favorable outcomes, and despite these being favorable subtypes of AML, the five year survival with traditional therapy has ranged between 40 to 60% across the globe. At MD Anderson Cancer Center, we have been evaluating a phase two clinical trial, which has now treated 200 patients, and we are showing the data of those 200 patients.

This includes an intensive regimen containing two nucleoside analogs that is fludarabine, Cytarabine, along with idarubicin or gemtuzumab ozogamicin, which is kind of a newer drug which has shown specifically benefit in this population of patients. What we show in our analysis is that when patients get treated with the flag go regimen, they have much better progression free survival and overall survival.

Five year overall survival is around 70 to 80%, which is a significant increase from the traditional 50% that we have seen with other regimens that have been used in previous studies or other centers. We do firmly believe that treating patients with intensified dual nucleoside analog based therapy, such as the Flag regimen, along with Gemtuzumab Ozogamicin, which is a specifically targeted drug use in acute myeloid leukemia, leads to favorable outcomes in patients with core binding factor AML and leads to very good long term survival outcomes, as well as deep molecular remissions leading to a very high cure fraction.

The next two studies I'll be talking about pertains to acute lymphoblastic leukemia, which is the other common type of acute leukemia. So traditionally, the outcomes of acute lymphoblastic leukemia in adults, that is, patients who are more than 18 years of age have been dismal compared to in the pediatric population. When we look at the adult group further closely, the outcomes have been particularly poor for patients who are more than 60 years of age.

And the primary reason for that being their inability to tolerate intensive chemotherapy and some other drugs like pegylated asparaginase, which are very important. But the adult people more than 60 years are not able to tolerate them by virtue of their age, and thus improvising available drugs to improve the depths of remission and long term outcomes in these group of patients is important.

We have been, conducting a phase two clinical trial with a low intensity chemotherapy regimen known as mini hyper CVD, to which a targeted drug called inotuzumab ozogamicin was added and in subsequent iteration to the protocol, Blinatumomab which is another targeted drug against a Cd19 protein present on the B-cells, were added. We are showing here the ten year median follow up data, one of the longest follow up of a clinical trial where we show very high five year progression free survival and overall survival of around 50%, one of the highest reported rates.

With such long term follow up and the continuous remission duration, that means the number of patients who remain in remission at five years was 70% and higher. Again, one of the highest, figures in this challenging population. We do feel that using targeted drugs like inotuzumab ozogamicin and Blinatumomab along with low intensity chemotherapy backbone, leads to the best depth and speed of responses in these group of patients, which translates to long term survival outcomes.

The second paper, or the second data that we are showing, is actually improvising further on this regimen that I spoke about. And completely removing chemotherapy. So I mentioned before that adult patients who are more than 60 years of age with acute lymphoblastic leukemia fare poorly, but those who are more than 70 years fare even further worse. So what do we do about them?

The main problem in these patients are they are not able to tolerate any chemotherapy. And the most common cause of death in these patients is not from the leukemia, but therapy related complications, infections, poor performance status, etc.. So to deliver a regimen to these patients which A is tolerable, B is efficacious, C does not lead to long term toxicity is prudent to improve their outcomes. Towards that approach, we have delivered a completely chemotherapy free regimen of inotuzumab ozogamicin a targeted drug against CD 22 protein on B cells and Blinatumomab, which is a targeted drug against Cd19, which is actually a T-cell engager. And with this combination, we show for the first time the first 14 patients who have been treated on this protocol.

And we see very good response rates, the durability of responses, as well as survival, though the follow up of the study is around a year. But at one year we are seeing overall survival of near 70%, which is very welcoming for a high risk group of patients beyond 70 years of age. With long term follow up, we expect that these survival curves to show long term maintenance of these outcomes.

And more importantly, we expect less mortality and morbidity from therapy related toxicity and thereby delivering the best outcome to these patients without leading to therapy related problems. Thank you.